Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck

A Phase II Trial of the HIV Protease Inhibitor Nelfinavir in Patients With Recurrent Symptomatic Adenoid Cystic Cancers of the Head and Neck

The purpose of this study is to evaluate the FDA-approved drug nelfinavir (NFV) as an oncologic agent for adenoid cystic cancers of the head and neck.

Specifically, subjects will be asked to take 1250 mg twice daily and follow-up with their medical oncologist as clinically indicated while taking this medication.

Subjects would be evaluated for quality of life issues utilizing the EORTC QLQ-C30 2-page questionnaire.

Subjects would also be evaluated clinically by the oncologist to determine if the NFV was having an anti-neoplastic effect.

The study remains unfunded. Therefore, potential subjects must be willing to provide self-travel to study site. This study requires a screening visit, initial study visit, and monthly follow-up. Subjects are not reimbursed for time, travel, or physician costs.

Study Overview

• Status: Completed
• Conditions: Head and Neck Neoplasms; Carcinoma, Adenoid Cystic
• Intervention / Treatment: Drug: Nelfinavir

Detailed Description

The hypothesis of this study is that nelfinavir, by inhibiting the Akt and MAPK pathways, can inhibit adenoid cystic carcinoid growth. These cancers are heavily dependent on these signalling pathways.

Adenoid cystic carcinomas (ACC) are rare and account for about 1% of all head and neck cancers. They stem from salivary glands and are known for their tendency to spread along nerve sheaths (perineural spread). ACC is known for its prolonged clinical course, multiple recurrence and the delayed onset of distant metastases. The median/mean age at presentation is 47-56. Although 5 year disease free survivals (DFS) are 65-70%, the 15 year DFS drops to 30-40%. If followed long enough, 35% of patients will eventually develop metastatic disease.

The most common treatment of ACC is surgery followed by post-operative radiotherapy. When ACC recurs, management options are often limited both by the morbidity and low efficacy of re-irradiation and repeated surgical resection. Reported response rates to chemotherapy are low and when it occurs, the duration of the response is short lived.

In an effort to explore possible targeted therapies for patients with recurrent ACC, Dr. Gupta's lab examined the activation of 3 signaling proteins (EGFR, Akt, and MAPK) in 9 different paraffinized tissue blocks. Initial indications from in vitro studies demonstrates NFV is tumoricidal at clinically achievable concentrations. To explore the clinical benefit of this FDA-approved medication, we seek to implement its off label use in patients who have failed all other therapies and have no other therapeutic options left.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The Holden Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological diagnosis of adenoid cystic carcinoma.
• Cancer should be staged recurrent or end-stage with/without metastases who have failed all other therapy.
• Age ≥ 18 years
• ECOG performance status 0-2 (Karnofsky ≥ 50%, see Appendix A).

• Patients must have normal organ and marrow function as defined below:

  • leukocytes ≥ 3,000/mm3
  • absolute neutrophil count ≥ 1,500/mm3
  • platelets ≥ 100,000/mm3
  • total bilirubin < 1.5 mg/dl OR a stable or a decreasing bilirubin in patients who have undergone placement of an intrabiliary stent
  • AST(SGOT) ≤ 2.5 X institutional upper limit of normal
  • ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
  • creatinine < 1.5 X institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• No known HIV infection. Since NFV is used in HIV patients, we do not want to interfere with the therapy the patient may already be on.
• Not pregnant. The effects of NFV on the developing human fetus have been studied in HIV positive women (21). We do not, however, know the risks along with radiation. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to NFV.
• Uncontrolled diabetes.
• Hemophilia A & B as increased bleeding during protease inhibitor therapy has been reported (22).
• Patients may not be receiving any other investigational agents. concomitant medications counterindicated for use with nelfinavir
• Pregnant or lactating women: The effects of NFV on the developing human fetus have been studied in HIV positive women (21). In addition, the chemotherapy will be deleterious to the fetus.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with NFV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nelfinavir; 1250 mg Nelfinavir twice daily Monday-Sunday	Drug: Nelfinavir; 1250 mg Nelfinavir twice daily Monday - Sunday

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Progression	Tumor progression as defined by RECIST version v1.1 criteria with ordinal measurements of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).	Every 1 to 3 months

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: Holden Comprehensive Cancer Center

Publications and helpful links

General Publications

• Gupta AK, Wilke WW, Taylor EN, Bodeker KL, Hoffman HT, Milhem MM, Buatti JM, Robinson RA. Signaling pathways in adenoid cystic cancers: implications for treatment. Cancer Biol Ther. 2009 Oct;8(20):1947-51. doi: 10.4161/cbt.8.20.9596. Epub 2009 Oct 22.
• Hoover AC, Milhem MM, Anderson CM, Sun W, Smith BJ, Hoffman HT, Buatti JM. Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial. Head Neck. 2015 May;37(5):722-6. doi: 10.1002/hed.23664. Epub 2014 Jun 18.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2009
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: February 8, 2010
• First Submitted That Met QC Criteria: February 8, 2010
• First Posted (Estimate): February 9, 2010

Study Record Updates

• Last Update Posted (Actual): October 9, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Nelfinavir
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Adenoid Cystic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Nelfinavir
• Other Study ID Numbers: 200905704

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No